PROJECT SUMMARY Focal brain lesions often result in disruption of brain network architecture and cause significant cognitive im- pairment and disability. Despite extensive research into human brain connectivity, fundamental questions re- main about how patterns of static functional connectivity are related to the brain dynamics (changes in activity over time) which ultimately give rise to thought and action. This is a signi?cant barrier to scienti?c progress, because until connectivity-dynamics associations have been better characterized, cognitive and systems neu- roscience will lack key knowledge necessary to continue developing robust theories of brain function. The ob- jective of the proposed research is to provide important new insight into the relationship between brain connec- tivity and dynamics, and to inform our understanding of how regional and distributed brain dynamics are im- pacted by?and reorganized after?focal brain damage. This research will use resting fMRI data from healthy individuals and patients with focal brain lesions to test the hypothesis that brain dynamics are shaped by func- tional connectivity at multiple spatial scales. Prior studies have shown that damage to highly connected ?hub? regions disrupts the modular architecture of functional brain networks. Multiple computational simulations fur- ther predict that brain connectivity plays a critical role in shaping brain dynamics, but empirical evidence is lacking and these predictions have never been empirically tested in humans. Guided by this past work, as well as promising preliminary data, two specific aims will: 1) Investigate the relationship between regional connec- tivity and dynamics, and 2) Determine the impact of hub damage on distributed brain dynamics. The first aim will explore the extent to which a brain region's whole-brain connectivity profile shapes how its activity fluctu- ates over time, while the second aim will investigate if highly connected hub regions play a critical role in shap- ing distributed brain dynamics. The proposed research is innovative in its use of analytic techniques from graph theory, information theory, and dynamical systems to ask fundamental questions about human brain or- ganization in health and disease. It is significant because it will provide insight into the functional organization of the human brain and has the potential to inform the development of novel diagnostic assessments and treatments for brain dysfunction and cognitive impairment following focal brain injury. In addition to the pro- posed research, a comprehensive training plan will provide the applicant with significant additional skills and experience in the collection of high-quality MRI data, studies of neurological patients, and the use of analytic techniques from graph theory, information theory, and dynamical systems. A rich scientific training environment at a world class university will be complimented by formal coursework, technical trainings, research experience and 1-on-1 mentoring with multiple expert faculty members. This training will directly contribute to the contin- ued growth of the applicant as an productive independent researcher and academic scientist.